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首页> 外文期刊>Nanotechnology >Synthesis and biological evaluation of 2.4nm thiolate-protected gold nanoparticles conjugated to Cetuximab for targeting glioblastoma cancer cells via the EGFR
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Synthesis and biological evaluation of 2.4nm thiolate-protected gold nanoparticles conjugated to Cetuximab for targeting glioblastoma cancer cells via the EGFR

机译：将2.4Nm硫醇硫酸盐保护的金纳米颗粒缀合的合成和生物学评价，其通过EGFR缀合西滕昔单抗靶向胶质母细胞瘤癌细胞

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摘要

Therapeutic monoclonal antibodies benefit to patients and the conjugation to gold nanoparticles (AuNPs) might bring additional activities to these macromolecules. However, the behavior of the conjugate will largely depend on the bulkiness of the AuNP and small sizes are moreover preferable for diffusion. Water-soluble thiolate-protected AuNPs having diameters of 2-3 nm can be synthesized with narrow polydispersity and can selectively react with incoming organic thiols via a S(N)2-like mechanism. We therefore synthesized a mixed thionitrobenzoic acid-, thioaminobenzoic acid-monolayered AuNP of 2.4 nm in diameter and developed a site-selective conjugation strategy to link the AuNP to Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody used in clinic. The water-soluble 80 kDa AuNP was fully characterized and then reacted to the hinge area of Cetuximab, which was selectively reduced using mild concentration of TCEP. The conjugation proceeded smoothly and could be analyzed by polyacrylamide gel electrophoresis, indicating the formation of a 1:1 AuNP-IgG conjugate as the main product. When added to EGFR expressing glioblastoma cells, the AuNP-Cetuximab conjugate selectively bound to the cell surface receptor, inhibited EGFR autophosphorylation and entered into endosomes like Cetuximab. Altogether, we describe a simple and robust protocol for a site-directed conjugation of a thiolate-protected AuNP to Cetuximab, which could be easily monitored, thereby allowing to assess the quality of the product formation. The conjugated 2.4 nm AuNP did not majorly affect the biological behavior of Cetuximab, but provided it with the electronic properties of the AuNP. This offers the ability to detect the tagged antibody and opens application for targeted cancer radiotherapy.
机译：治疗性单克隆抗体对患者的益处和金纳米颗粒（AUNP）的缀合可能为这些大分子带来额外的活动。然而，缀合物的行为在很大程度上取决于AUNP的大部分，并且还优选用于扩散的小尺寸。具有2-3nm直径的水溶性硫醇保护的AuNP可以用窄的多分散性合成，并且可以通过S（n）2样机制选择性地与进入的有机硫醇反应。因此，我们合成了直径为2.4nm的混合硫苯二苯甲酸 - ，硫代氨基苯二苯甲酸 - 单层AUNP，并开发了一种位点选择性缀合策略，以将AUNP与临床中使用的抗表皮生长因子受体（EGFR）抗体联系起来。水溶性80kDaαUnp完全表征，然后反应到西妥昔单抗的铰链区域，使用温和的TCEP选择性地减少。共轭平稳地进行，可以通过聚丙烯酰胺凝胶电泳分析，表明形成1：1 AUNP-IgG缀合物作为主要产物。当添加到表达胶质母细胞瘤细胞的EGFR时，选择性地与细胞表面受体结合的AUNP-CETUXIMAB缀合物抑制EGFR自磷酸化并进入甲磺酸中的底皮体。总共，我们描述了一种简单且坚固的方案，用于将硫醇保护的AUNP的硫醇保护的AUNP与西妥昔单抗的定向缀合，这可以很容易地监测，从而允许评估产品形成的质量。缀合的2.4nm aUnp没有大大影响西汀昔单抗的生物学行为，而是提供了与AUNP的电子性质提供。这提供了检测标记抗体的能力，并打开靶向癌症放射疗法的应用。

著录项

  • 来源
    《Nanotechnology》 |2019年第18期|共13页
  • 作者

    Groysbeck Nadja; Stoessel Audrey; Donzeau Mariel; da Silva Elisabete Cruz; Lehmann Maxime; Strub Jean-Marc; Cianferani Sarah; Dembele Kassioge; Zuber Guy;

  • 作者单位

    Univ Strasbourg CNRS UMR 7242 Lab Biotechnol &

    Signalisat Cellulaire Blvd Sebastien Brant F-67400 Illkirch Graffenstaden France;

    Univ Strasbourg CNRS UMR 7242 Lab Biotechnol &

    Signalisat Cellulaire Blvd Sebastien Brant F-67400 Illkirch Graffenstaden France;

    Univ Strasbourg CNRS UMR 7242 Lab Biotechnol &

    Signalisat Cellulaire Blvd Sebastien Brant F-67400 Illkirch Graffenstaden France;

    Univ Strasbourg CNRS UMR 7021 Lab Bioimagerie &

    Pathol Fac Pharm F-67401 Illkirch Graffenstaden France;

    Univ Strasbourg CNRS UMR 7021 Lab Bioimagerie &

    Pathol Fac Pharm F-67401 Illkirch Graffenstaden France;

    Univ Strasbourg CNRS UMR 7178 IPHC Lab Spectrometrie Masse BioOrgan F-67000 Strasbourg France;

    Univ Strasbourg CNRS UMR 7178 IPHC Lab Spectrometrie Masse BioOrgan F-67000 Strasbourg France;

    Univ Strasbourg IPCMS 23 Rue Loess F-67034 Strasbourg France;

    Univ Strasbourg CNRS UMR 7242 Lab Biotechnol &

    Signalisat Cellulaire Blvd Sebastien Brant F-67400 Illkirch Graffenstaden France;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 特种结构材料;
  • 关键词

    gold nanoparticle; site-directed bioconjugation; antibody; targeted cancer therapy; epidermal growth factor receptor;

    机译：金纳米粒子;植物指导的生物谐波;抗体;靶向癌症治疗;表皮生长因子受体;

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